High-dose acute exposure of paraquat induces injuries of swim bladder, gastrointestinal tract and liver via neutrophil-mediated ROS in zebrafish and their relevance for human health risk assessment.

The exact toxicological mechanisms of paraquat (PQ) poisoning are not entirely clear, especially on the high-level acute exposure. To assess the health risk of PQ, especially to suicidal individuals, accidental ingestion eaters, occupational groups, and special multitude, firstly we explored the acute toxic effect and the possible mechanisms of high-level exposure of PQ using zebrafish. The mainly target organs of PQ were swim bladder which is the homolog of the mammalian lung, followed by gastrointestinal tract and liver. Morphological malformations which were further defined by histopathologic examination include smaller size, fibrosis and inflammatory cell invasion for swim bladder; irregularly arranged or dissolved epithelial folds, loss of villous architecture, and ecclasis of mucosal cells in a smaller lumen for gastrointestinal tract; as well as smaller size, degeneration, fibrous proliferation, atrophy for liver. In addition, PQ enhanced leukocyte recruitment (neutrophil migrated first, followed by macrophage) into swim bladder and induced ROS which can be scavenged by glutathione. Moreover, qRT-PCR results showed that PQ increased the expression level of genes involved in the inflammatory response, such as L-1ß, IL-6, IL-8, TNF-α, TNF-ß, IFN-1, TGF-ß, and NF-kB. For the first time, our results demonstrated that acute exposure of PQ induced pulmonary toxicity which was followed by gastrointestinal and hepatic toxicity via neutrophil-mediated ROS in zebrafish. In summary, these findings generated here will contribute to our better understanding of characteristics of PQ acute poisoning and can provide valuable information on better PQ poisoning treatments, occupational disease prevention, and providing theoretical foundation for risk management measures.

Assessment of immunotoxicity of dibutyl phthalate using live zebrafish embryos.

This study set out to understand the immune-toxic effects of dibutyl phthalate (DBP) using transgenic, albino or AB line zebrafish. Zebrafish embryos were exposed to different concentrations of DBP, and the immune cells formation, phagocytosis ability were measured after a short-term exposure to DBP for 6 h post-fertilization (hpf) to 72 or 96 hpf. Exposure to DBP was found to inhibit the neutrophils and macrophage formation in a concentration-dependent manner. The ability of macrophage phagocytosis was all decreased after exposure to DBP, indicating the occurrence of immunotoxicity. The respiratory burst was induced, and the transcription levels of T/B cell-related genes rag1/2 were up-regulated. The overall results indicate that DBP in aquatic environment greatly influence the immune system in fish, and zebrafish embryos can serve as a reliable model for the developmental immunotoxicity of toxic-chemicals.